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Tuesday, January 15, 2013

Lassa Hemorrhagic Fever

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This week at Infection Landscapes we begin to discuss the last group of viruses to be considered in this extended series on hemorrhagic fevers: the arenaviruses. In general, there is a greater prevalence of human infection in endemic areas than the other viruses causing hemorrhagic fevers that we have discussed in this series. We begin the section on arenaviruses with Lassa fever and follow next time with the American areanaviruses.

Lassa fever is named after the town of Lassa in Nigeria where the disease was first documented in 1969.

The Pathogen. Lassa virus (LASV) is a member of the Arenaviridae family. These are enveloped viruses approximately 120 nanometers in diameter with single-stranded, ambisense RNA genomes in two segments:

Monocytes, macrophages, dendritic cells, and endothelial cells are the target cells for LASV. A membrane-bound glycoprotein (GP1) binds to the host receptor, and the virus enters the cell by endocytosis. Replication occurs in the cytoplasm of the host cell. Pathogenesis follows suppression of specific lymphocyte, platelet, and endothelial functions, rather than stimulating a hyper-inflammatory response. This results in the suppression of specific cytokines, diminished coagulation, and vascular leakage and hemorrhaging.

The Reservoir. The rodent, Mastomys natalensis, is the natural reservoir host for LASV:

Mastomys natalensis

Known as the common African rat, this rat is extraordinarily widespread throughout incredibly varied landscapes across sub-Saharan Africa. It can be found in tropical or subtropical dry and moist lowland forest, dry and moist savanna, tropical or subtropical dry and moist shrubland, agricultural land of varied type, and urban settings. As such, this reservoir is well adapted to both sylvan and domestic landscapes and thus acts a a robust reservoir for human transmission.

The Disease. Most LASV infections are asymptomatic. Between 9% and 26% of those infected will present with clinical symptoms. While a minority, these individuals typically experience severe disease. Approximately 1 to 3 weeks after initial infection, those developing clinically apparent Lassa hemorrhagic fever (LHF) typically present with fever, malaise, chills, and, commonly, a sore throat that is may be exudative. Following these initial symptoms, myalgia, arthralgia, headache, and cough are common. Abdominal pain with diarrhea and vomiting are also common. Renal dysfunction with frank proteinuria can present. Myocarditis and nose, gum, and pulmonary bleeding may follow. Petechiae can present on the trunk and neck. Moderate infections begin to resolve after approximately one week, while more severe infections continue to progress. Advanced complications can include bradycardia, extensive face and neck edema, mucosal and conjunctival bleeding, pleural effusion, encephalopathy, and hepatitis. Neurologic complications may include intention tremors, followed later by seizures.Vascular leakage and hemorrhage can lead to shock and death. The overall mortality for all infections is estimated at about 1%. However, among those hospitalized for their infections, the mortality is between 15% and 20%, and can be as high as 60% among those with severe infections who receive no medical attention.

In addition, long term disability is common in those with symptomatic LHF. The most common disability suffered is hearing loss. Approximately 25% who develop symptomatic disease will experience some degree of deafness due to the involvement of the eighth cranial nerve during infection. Incomplete hearing is recovered in only about 50% of these cases. The remainder suffer permanent hearing loss.

The Epidemiology and the Landscape. The primary mode of transmission for LASV is from infected rodents to humans via the airborne route, by direct contact with excretory substances containing virus that are shed from the reservoir host, or through a contaminated common vehicle, such as water or food. The virus is shed in the stool and urine of the rodent reservoirs and, when dust containing dried excreta is disturbed, can be inhaled by the human host. Lassa virus can also be transmitted directly from person to person by way of contaminated blood or body fluid exposure. This mode of transmission can be important for nosocomial spread of LASV, particularly during outbreaks. Finally, transmission from rodent to human can occur by way of a rat bite or, as these rodents are a delicacy in many endemic areas, during the processing or eating of infected rodents.

There are between 100,000 and 500,000 incident cases of LHF each year and about 5,000 deaths, making this the most common, though narrowly distributed, hemorrhagic fever to affect humans. Endemicity is limited to several countries in West Africa.

The landscape of LASV infection is delineated primarily by the generalized range of the reservoir rodent host and the specific points of contact with humans, which often intersect agricultural or domestic human spaces, determine local cultural preferences and/or practices, or generate sources of rodent contamination of food or water. The latter can be particularly important in areas with poor sanitation and water infrastructure, which are often the same areas endemic for LASV.

Another important important feature of this landscape is defined by person to person transmission. In this context, the essential human function of caring for the sick, whether in the home or in a clinical setting, can expand endemic rodent to human transmission into epidemic human to human transmission.

Control and Prevention. Because the reservoir host is ubiquitous in endemic areas, elimination of the reservoir is not possible. However, rodent control is still an important strategy to control LASV infection in humans. Taking precautions to eliminate safe spaces for rodents in the home or other structures of human habitation or occupation can reduce effective human to rodent contact and thus block this important mode of LASV transmission.

In order to eliminate safe spaces for mice the following steps can be employed:

Remove all food sources: Food and garbage should always be kept in well-sealed containers that cannot be breached by rodents. In addition, pet food and/or garden fruit and vegetables left unattended outside will often attract rodents.

Household maintenance: Good maintenance both inside and outside the home can be very important in eliminating rodent habitat. On the outside, overgrown plants and shrubs, unattended woodpiles or debris, and unattended outdoor structures can all serve as welcome homes for rodents, and should be be regularly maintained. On the inside, poorly sealed foundations, roofing, vents, and other household structures can provide easy access to the interior of the house and thus provide good rodent habitat. As such, it is very important to maintain good structural integrity of the house to keep the rodents out.

During outbreaks, or in any endemic health care setting, blocking nosocomial transmission by employing good barrier protection and patient isolation can also be very important in preventing LASV spread from infected patients to health care personnel and/or other non-infected patients.

12 comments:

Hi Michael. Was really impressed with your summary of Lassa fever, particularly the prevention and control section. I think it's important to keep in mind that the epidemiology of Lassa fever is very much unknown and much of what is reported on rodent-to-rodent and rodent-to-human transmission, incidence, mortality and virus distribution is really based on limited to no empirical data. This is likely the case with many diseases, but I just wanted to throw that out there.

This was a very interesting disease! The high rate of asymptomatic persons is unnerving, as well as the severity of disease. The incubation period for those who do present symptoms is also a good amount of time. It was a relief to see death rate is very low in comparison to other diseases.

I wonder to what extent asymptomatic persons can infect others. What is the latency period for Lassa Fever in asymptomatic and symptomatic people? Also, can asymptomatic persons spread the disease? Lastly, can Lassa Fever lie dormant until a later point in life when it is triggered into full pathogenesis?

Majority ineffective are asymptomatic, often the closest clinic or hospital is miles away by then it may be too late. Could there be an under reporting in the death rate and maybe the rate may be more or roughly same in comparison to other hemorrhagic fevers?

What I find alarming about Lassa fever is the fact that it can be transmitted in a variety of environmental landscapes from dry lands, tropical or moist areas, and even urban settings. This means that creating a plan for protection against the reservoir would have to be tailored to every specific area that they are found, thus meaning more funding for research on how to properly prevent or limit contact between these rodents and humans in a number of settings. Since the early signs are asymptomatic, I am curious if there are any treatments specific to Lassa fever that would prevent someone who is at greater risk for the infection, such as an elderly person, from reaching the intense stages of the infection? Or are the symptoms usually recognized as Lassa fever not until it progresses until the later stages?

Early stages of infection with the Lassa virus can result in a wide range of symptoms causing misdiagnoses with influenza, malaria and other febrile illnesses. The only drug, Ribavirin, that's used to treat infection is only useful up to six days after disease onset. Some of the infected, feel better after 7 days (also contributing to misdiagnosis), however others infected progress to show severe symptoms of the disease when its much too late for treatment.

In 2012 Lassa fever Killed about 40 Nigerian and spread across the country and average of 380 were infected and the Nigerian government had to create a Lassa fever rapid response team, in fact two nurses died during the same outbreaks.One of the dangerous ways of transmission is when the Mastomys rats live inside peoples home and leave their execration in the food storage, while the disease is some what controlled in the west the mortality rate is almost 50%

Hi Khalid! Hope all is well. It’s very interesting to know that as a result of the significant number of deaths from Lassa fever in 2012, Nigeria created a response team. It would be interesting to know what intervention and prevention methods were implemented as a result. This disease is the first I’ve come across which is transmitted to humans from contacts with food or household items contaminated with rodent waste. Since it appears that these African rats are accustomed to enter the homes of some residents, what assistance is the government providing to prevent infestation? I know that dependent upon the surrounding environment sometimes having rodents in the home is inevitable (even with proper home maintenance and good structure). Given the occurrence of this disease in different parts of Africa, are homes monitored/evaluated in high-risk areas?

Hi Khalid, thanks so much for posting that piece of information! It's very unfortunate that Lassa fever still has such a large impact in the endemic areas. It's also interesting that the landscape of the environment and the human-environment interactions play an important role in the transmission of the disease. If we could control the population of the rats, or the interaction between the rats and human food storage, then we can probably make a very large impact on Lassa fever transmission.

Hello Khalid, you pose some interesting but yet alarming statistics on the number of cases/deaths due to Lassa fever in Nigeria. As a Nigerian-born immigrant, it breaks my heart to admit that the sanitary system in Nigeria is poorly organized and managed. Such flawed system makes it harder to protect food and wastage from rodent infestation. You made reference to the lassa fever in 2012 and unsurprisingly, there is another Lassa outbreak in Nigeria this year. According to the US & World Report News, doctors have identified 81 suspected cases since mid-November and 35 people have been killed by the virus. And again, rapid response teams have been deployed to distribute ribavirin, an antiviral drug for Lassa, to high-risk communities. Hopefully, Nigeria comes up with an effective strategy to assuage the presence of rodents in habitual spaces.